Quetiapine and its salts, particularly Quetiapine hemifumarate, have been employed as pharmaceutically active agents in the treatment of schizophrenia and bipolar mania.
Quetiapine fumarate is a psychotropic agent belonging to a chemical class of dibenzothiazepine derivatives. The chemical designation is 2-[2-(4-dibenzo[V][1,4]thiazepin-11-yl-1-piperazinyl)ethoxy]-ethanol fumarate (2:1) (salt). It is present in tablets as the fumarate salt.
U.S. Pat. No. 4,879,288 disclose the product Quetiapine and its pharmaceutically acceptable salt(s) along with preparation process.
Dosing regimens for antipsychotics is generally two or three tablets per day. These dosing regimens have proved disadvantageous because of lack of convenience, and more importantly, lack of compliance. Control of Quetiapine plasma levels is useful during treatment. For example, when a patient presents with acute psychosis, it may be desirable to introduce an immediate large dosage of Quetiapine, followed by the maintenance of sustained plasma level of Quetiapine. Single dosage forms that provide particular plasma profiles of Quetiapine are thus desirable. Many techniques have been used to provide sustained release pharmaceutical dosage forms in order to maintain therapeutic serum levels of medicaments and to minimize the effects of missed doses of drugs caused due to lack of patient compliance.
It is typically the goal of all sustained-release preparations to provide a longer period of pharmacological response after the administration of the dosage form than that which is ordinarily experienced after the administration of the immediate release dosage forms. Desirably the sustained release provides a generally uniform and constant rate of release over an extended period of time, which achieves a stable and desired blood (plasma) level of the active ingredient without the need for frequent administration of the medicament.
However, it is often not possible to readily predict whether a particular sustained release formulation will provide the desired sustained release of a relatively sparingly soluble to insoluble drug, and it has generally been found that it is necessary to carry out considerable experimentation to obtain sustained release formulations of such drugs having the desired bioavailability when ingested.
U.S. Pat. No. 5,948,437 disclose sustained release formulation of Quetiapine and its salt using gelling agents.
US 2005158383 is related to a dual retard solid dosage formulation comprising a matrix comprising a therapeutically effective amount of Quetiapine or a pharmaceutically acceptable salt thereof; and a wax material.
WO 2007/133583 A2 is related to a zero order modified release dosage form having a matrix core comprising hydrophobic agent, which acts as a release retardant and a modified release coating.
The recommended initial dose is 300 mg/day. Patients should be titrated within a dose range of 400-800 mg/day depending on the response and tolerance of the individual patient. Dose increases can be made at intervals as short as 1 day and increments of up to 300 mg/day.
For some patients, the Quetiapine dosage required for therapeutic effect is quite high, especially if a sustained release dosage form is administered. For example, the largest current dosage form is a 300 mg tablet, administered two or three times daily. Thus an equivalent once a day dosage form would contain high amount of Quetiapine.
When a high dosage of Quetiapine is combined with excipients, the resulting dosage form (e.g., tablets, capsules, etc.) may be considerably larger than is desirable. Also, the dosage form can be undesirably large when Quetiapine is combined with other active agents, especially other high dose active agents. The large size of these dosage forms can be difficult for patients, especially elderly patients, to swallow. Further, large dosage form size may increase the risk of choking upon oral administration and may reduce patient compliance.
Thus there exists a need for a dosage form comprising a high dose amount of Quetiapine that has a smaller size than the conventional dosage forms containing substantially the same dose amount of Quetiapine.
The present invention addresses these and other needs for improved Quetiapine dosage forms, particularly controlled release and/or sustained release dosage forms. The present invention relates to a pharmaceutical composition and more particularly to a sustained release pharmaceutical composition comprising Quetiapine or a pharmaceutically acceptable salt thereof.